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. 2021 Jun 8;11(11):2924–2943. doi: 10.1158/2159-8290.CD-20-1378

Figure 7.

Figure 7. Systemic AXL inhibition induces potent antileukemic immunity and eliminates leukemic blasts in AXL-negative leukemias. A and B, Kaplan–Meier survival curves of C57BL/6 WT mice (A) or NSG mice (B) challenged with 5.105 Asxl1−/− AML cells and treated with either vehicle or bemcentinib (50 mg/kg, twice daily). ns, not significant. ***, P < 0.001, log-rank (Mantel–Cox) test. C, Kaplan–Meier survival analysis of C57BL/6 WT mice challenged with 103 B-ALL cells and treated with either vehicle (n = 7) or nilotinib (80 mg/kg, once a day) plus bemcentinib (50 mg/kg, twice daily; n = 33) for a total of 44 days. Data are pooled from two independent experiments. ***, P < 0.001, log-rank (Mantel–Cox) test. D, Representative FACS plots depicting absence of GFP+ B220dim leukemic cells in the bone marrow of long-term survivors from C. E, Mice from C were followed by weekly bleeding. Three of 33 mice (#24, #26, and #31) showed GFP+ cells indicative of disease recurrence and were subjected to anti–PD-1 treatment as indicated (7 × 200 μg/mL every fourth day). Mouse #31 succumbed to full-blown leukemia on day 36, while #24 and #26 remained leukemia-free. F, Kaplan–Meier survival analysis of NSG mice challenged with 103 B-ALL cells and treated with either vehicle, nilotinib, or nilotinib plus bemcentinib for a total of 44 days as in C. ns, not significant, log-rank (Mantel–Cox) test. G, WT mice were injected with 103 TKIR B-ALL cells. After 5 days, mice were randomly attributed to the indicated vehicle or treatment groups and their survival depicted using a Kaplan–Meier analysis. Data are pooled from two independent experiments. ns, not significant, **, P < 0.01; ****, P < 0.0001, log-rank (Mantel–Cox) test. H, Representative FACS plots depicting absence of GFP+ B220dim leukemic cells in the bone marrow of bemcentinib + vincristine–treated long-term survivors from G. In all experiments, treatments were initiated and stopped on the days indicated by dotted lines.

Systemic AXL inhibition induces potent antileukemic immunity and eliminates leukemic blasts in AXL-negative leukemias. A and B, Kaplan–Meier survival curves of C57BL/6 WT mice (A) or NSG mice (B) challenged with 5.105Asxl1−/− AML cells and treated with either vehicle or bemcentinib (50 mg/kg, twice daily). ns, not significant. ***, P < 0.001, log-rank (Mantel–Cox) test. C, Kaplan–Meier survival analysis of C57BL/6 WT mice challenged with 103 B-ALL cells and treated with either vehicle (n = 7) or nilotinib (80 mg/kg, once a day) plus bemcentinib (50 mg/kg, twice daily; n = 33) for a total of 44 days. Data are pooled from two independent experiments. ***, P < 0.001, log-rank (Mantel–Cox) test. D, Representative FACS plots depicting absence of GFP+ B220dim leukemic cells in the bone marrow of long-term survivors from C. E, Mice from C were followed by weekly bleeding. Three of 33 mice (#24, #26, and #31) showed GFP+ cells indicative of disease recurrence and were subjected to anti–PD-1 treatment as indicated (7 × 200 μg/mL every fourth day). Mouse #31 succumbed to full-blown leukemia on day 36, while #24 and #26 remained leukemia-free. F, Kaplan–Meier survival analysis of NSG mice challenged with 103 B-ALL cells and treated with either vehicle, nilotinib, or nilotinib plus bemcentinib for a total of 44 days as in C. ns, not significant, log-rank (Mantel–Cox) test. G, WT mice were injected with 103 TKIR B-ALL cells. After 5 days, mice were randomly attributed to the indicated vehicle or treatment groups and their survival depicted using a Kaplan–Meier analysis. Data are pooled from two independent experiments. ns, not significant, **, P < 0.01; ****, P < 0.0001, log-rank (Mantel–Cox) test. H, Representative FACS plots depicting absence of GFP+ B220dim leukemic cells in the bone marrow of bemcentinib + vincristine–treated long-term survivors from G. In all experiments, treatments were initiated and stopped on the days indicated by dotted lines.